A key role for leukemia inhibitory factor in C26 cancer cachexia

Cachexia is an exacerbating event in many types of cancer that is strongly associated with a poor prognosis. We have identified cytokine, signaling, and transcription factors that are required for cachexia in the mouse C26 colon carcinoma model of cancer. C2C12 myotubes treated with conditioned medium from C26 cancer cells induced atrophy and activated a STAT-dependent reporter gene but not reporter genes dependent on SMAD, FOXO, C/EBP, NF-κB, or AP-1. Of the gp130 family members IL-11, IL-6, oncostatin M (OSM), and leukemia inhibitory factor (LIF), only OSM and LIF were sufficient to activate the STAT reporter in myotubes. LIF was elevated in C26 conditioned medium (CM), but IL-6, OSM, TNFα, and myostatin were not. A LIF-blocking antibody abolished C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and myotube atrophy but blocking antibodies to IL-6 or OSM did not. JAK2 inhibitors also blocked C26 CM-induced STAT reporter activation, STAT3 phosphorylation, and atrophy in myotubes. LIF at levels found in the C26 CM was sufficient for STAT reporter activation and atrophy in myotubes. In vivo, an increase in serum LIF preceded the increase in IL-6 in mice with C26 tumors. Overexpression of a dominant negative Stat3Cβ-EGFP gene in myotubes and in mouse muscle blocked the atrophy caused by C26 CM or C26 tumors, respectively. Taken together, these data support an important role of LIF-JAK2-STAT3 in C26 cachexia and point to a therapeutic approach for at least some types of cancer cachexia.R01 AR060217 - NIAMS NIH HHS; UL1 TR000157 - NCATS NIH HHS; UL1-TR000157 - NCATS NIH HHShttp://www.jbc.org/content/290/32/19976.full.pdf?sid=936d126d-814b-4f54-961d-0e98caa31314Published versio

Gravitino dark matter from increased thermal relic particles

We investigate the so-called superWIMP scenario with gravitino as the lightest supersymmetric particle (LSP) in the context of non-standard cosmology, in particular, brane world cosmology. As a candidate of the next-to-LSP (NLSP), we examine slepton and sneutrino. Brane world cosmological effects dramatically enhance the relic density of the slepton or sneutrino NLSP, so that the NLSP with mass of order 100 GeV can provide the correct abundance of gravitino dark matter through its decay. We find that with an appropriate five dimensional Planck mass, this scenario can be realized consistently with the constraints from Big Bang Nucleosynthesis (BBN) for both NLSP candidates of slepton and sneutrino. The BBN constraints for slepton NLSP are more stringent than that for sneutrino, as the result, the gravitino must be rather warm in the slepton NLSP case. The energy density of gravitino produced by thermal scattering is highly suppressed and negligible due to the brane world cosmological effects.Comment: 15 pages, discussion and references added, the final versio

Reheating and gravitino production in braneworld inflation

We consider the constraints that can be imposed on a wide class of Inflation models in modified gravity scenarios in which the Friedmann equation is modified by the inclusion of $\rho^2$ terms, where $\rho$ is the total energy density. In particular we obtain the reheating temperature and gravitino abundance associated with the end of inflation. Whereas models of chaotic inflation and natural inflation can easily avoid the conventional gravitino overproduction problem, we show that supersymmetric hybrid inflation models (driven by both F and D-terms) do not work in the $\rho^2$ dominated era. We also study inflation driven by exponetial potentials in this modified background, and show that the gravitino production is suppressed enough to avoid there being a problem, although other conditions severely constrain these models.Comment: 24page

Light wino dark matter in brane world cosmology

The thermal relic density of the wino-like neutralino dark matter in the brane world cosmology is studied. The expansion law at a high energy regime in the brane world cosmology is modified from the one in the standard cosmology, and the resultant relic density can be enhanced if the five dimensional Planck mass $M_5$ is low enough. We calculate the wino-like neutralino relic density in the anomaly mediated supersymmetry breaking scenario and show that the allowed region is dramatically modified from the one in the standard cosmology and the wino-like neutralino with mass of order 100 GeV can be a good candidate for the dark matter. Since the allowed region disappears eventually as $M_5$ is decreasing, we can find a lower bound on $M_5 \gtrsim 100$ TeV according to the neutralino dark matter hypothesis, namely the lower bound in order for the allowed region of the neutralino dark matter to exist.Comment: 16 pages, 9 figures, final versio

Correlation analysis of stochastic gravitational wave background around 0.1-1Hz

We discuss prospects for direct measurement of stochastic gravitational wave background around 0.1-1Hz with future space missions. It is assumed to use correlation analysis technique with the optimal TDI variables for two sets of LISA-type interferometers. The signal to noise for detection of the background and the estimation errors for its basic parameters (amplitude, spectral index) are evaluated for proposed missions.Comment: 11 pages, 7 figures, revised version, to appear in PR

Neutralino dark matter in brane world cosmology

The thermal relic density of the neutralino dark matter in the brane world cosmology is studied. Since the expansion law at a high energy regime in the brane world cosmology is modified from the one in the standard cosmology, the resultant relic density can be altered. It has been found that, if the five dimensional Planck mass $M_5$ is lower than $10^4$ TeV, the brane world cosmological effect is significant at the decoupling time and the resultant relic density is enhanced. We calculate the neutralino relic density in the Constrained Minimal Supersymmetric Standard Model (CMSSM) and show that the allowed region is dramatically modified from the one in the standard cosmology and eventually disappears as $M_5$ is decreasing. We also find a new lower bound on $M_5 \gtrsim 600$ TeV based on the neutralino dark matter hypothesis, namely the lower bound in order for the allowed region of the neutralino dark matter to exist.Comment: 12 pages, 8 figure

Gravitational Wave Astrometry for Rapidly Rotating Neutron Stars and Estimation of Their Distances

We discuss an astrometric timing effect on data analysis of continuous gravitational waves from rapidly rotating isolated neutron stars. Special attention is directed to the possibility of determining their distances by measuring the curvature of the wave fronts. We predict that if continuous gravitational waves from an unknown neutron star with a stable rotation are detected around 1kHz within 1/3yr by initial LIGO detectors and the ellipticity parameter epsilon is smaller than 10^{-6}, the distance r to the source can be estimated with relative error \Delta r/r of \sim 10% by using the broad band configuration of advanced LIGO detectors over 3 years. By combining the observed amplitude of the waves with the estimated distance, information on the parameter $\epsilon$ can be obtained purely through gravitational wave measurements.Comment: 6 pages, 1 figure, to appear in PR

A case study on developing a teacher\u27s capacity in mathematical modelling

Research has indicated that for teachers to facilitate mathematical modelling activities in the mathematics classroom, they need to be familiar with the process of mathematical modelling. As such, it is imperative that teachers experience the whole mathematical modelling process. This paper reports on a Multi-tiered Teaching Experiment designed to help a teacher develop his capacity in the domain of mathematical modelling. Drawing on part of a larger case-based study conducted using Design Research phases situated within the Multi-tiered Teaching Experiment framework, the purpose of this paper is to exemplify how the research design fostered growth in teacher capacity through the natural development of critical moments of learning by the teacher during interactions between the researchers and the teacher-modeller himself. The potential of the Multi-tiered Teaching Experiment as a useful non-prescriptive teacher development approach building upon the existing repertoire of individual teachers will be discussed

Thermal leptogenesis in brane world cosmology

The thermal leptogenesis in brane world cosmology is studied. In brane world cosmology, the expansion law is modified from the four-dimensional standard cosmological one at high temperature regime in the early universe. As a result, the well-known upper bound on the lightest light neutrino mass induced by the condition for the out-of-equilibrium decay of the lightest heavy neutrino, $\tilde{m}_1 \lesssim 10^{-3}$ eV, can be moderated to be $\tilde{m}_1 \lesssim 10^{-3} {eV} \times (M_1/T_t)^2$ in the case of $T_t \leq M_1$ with the lightest heavy neutrino mass ($M_1$) and the ``transition temperature'' ($T_t$), at which the modified expansion law in brane world cosmology is smoothly connecting with the standard one. This implies that the degenerate mass spectrum of the light neutrinos can be consistent with the thermal leptogenesis scenario. Furthermore, as recently pointed out, the gravitino problem in supersymmetric case can be solved if the transition temperature is low enough $T_t \lesssim 10^{6-7}$ GeV. Therefore, even in the supersymmetric case, thermal leptogenesis scenario can be successfully realized in brane world cosmology.Comment: 9 pages, final versio